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ICCVAM Biennial Report 2018-2019

Biennial Progress Report 2018-2019 Interagency Coordinating Committee on the Validation of Alternative Methods

High-throughput In Vitro to In Vivo Extrapolation Using Tox21 Data

This NIEHS project developed and refined approaches to extrapolate all Tox21 chemical-concentration effect data to estimate human-equivalent exposure doses. The effort built on previous efforts using high-throughput toxicokinetics models and combined them with in silico-estimated parameters. A publicly available web application based on these methods is available through the Tox21 Toolbox on the NTP public website. NIEHS is continuing to refine the models for use in research and chemical screening prioritization. Additionally, a simple IVIVE workflow allowing users to select Tox21 assays and chemicals and extrapolate to estimated exposures is available in the NICEATM Integrated Chemical Environment (ICE). The ICE IVIVE tool provides three models with varied complexity and exposure routes: a one-compartment PK model, a three-compartment PK model, and a multi-compartment physiologically based PK model for oral and intravenous routes. These models use the ICE curated Tox21 data to predict equivalent administered in vivo doses for acute oral toxicity and endocrine disruption endpoints.